An estimated two million people a year are affected by arterial and venous thrombosis. Treatment with thrombolytic drugs is effective, but current procedures are successful at rapidly dissolving the thrombi only 70% to 80% of the time. The applicant organization, EKOS, has developed an ultrasound catheter device and demonstrated an enhanced thrombolytic effect in vitro and in vivo. The underlying acoustic and biochemical mechanisms for this enhancement are unknown. Understanding the fundamental mechanisms of ultrasound-assisted drug transport through clots is critical for optimizing the ultrasound catheter device and protocols for its use. The specific aims are: 1. Develop a confocal and epifluorescence imaging system to visualize in vitro fibrin clots under conditions of lysis and regimens of catheter-delivered ultrasound, and to test and optimize different probe designs; 2. Characterize the action of catheter delivered ultrasound of varying intensity and frequency on the penetration and binding rates of fluorescently labeled problems into purified fibrin gels and in vitro clots; and 3. Develop a computer algorithm that will: (1) provide theoretical upper limits for ultrasound-assisted thrombolysis; (2) facilitate compute aided design of improved catheter geometry and operation; and, (3) facilitate in- house technology transfer of knowledge gained with thrombolysis to new applications for ultrasound catheters. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE